Clinical development of 18F PET tracer for imaging VEGF receptors

DESCRIPTION provided by applicant The overall goal of this collaborative Fast Track project is clinical development of a novel F PET tracer for molecular imaging of receptors for vascular endothelial growth factor VEGFR This receptor is the major anti angiogenic drug target in oncology patients Critically VEGFR prevalence decreases when VEGF VEGFR anti angiogenic inhibitors andquot workandquot and increases when these drugs stop andquot workingandquot These findings provide a rationale for VEGFR imaging for image guided anti angiogenic therapy To provide for high selectivity specificity and VEGFR mediated intracellular accumulation the F PET tracer will be targeted by VEGFR ligand scVEGF The protein will be site specifically derivatized with a strained alkyne for copper free click chemistry radiolabeling with F PEG aside In Phase I of this project we will select the lead scVEGF Alkyne conjugate optimize conditions for F radiolabeling and validate the use of lead tracer for monitoring anti angiogenic therapy in a murine model of triple negative breast cancer In Phase II we will produce cGMP grade conjugate undertake FDA required toxicology and dosimetry studies and proceed to Phase I clinical trials in healthy volunteers PUBLIC HEALTH RELEVANCE We propose to develop a novel first in class F PET tracer for molecular imaging of receptors for vascular endothelial growth factor which are the major drug targets in tumor neovasculature The Fast Track project involves preclinical development of click chemistry F radiolabeling of a novel protein based conjugate cGMP production pre clinical toxicology dosimetry and Phase I clinical trials in healthy volunteers